Clinicopathologic and Molecular Genetic Features of Spindle Cell Rhabdomyosarcoma harboring ZFP64::NCOA2/3 fusions: A Series of 14 Cases

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F25%3A10503958" target="_blank" >RIV/00216208:11140/25:10503958 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=VkeXFIq4Cc" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=VkeXFIq4Cc</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.modpat.2025.100906" target="_blank" >10.1016/j.modpat.2025.100906</a>

Result language

angličtina

Original language name

Clinicopathologic and Molecular Genetic Features of Spindle Cell Rhabdomyosarcoma harboring ZFP64::NCOA2/3 fusions: A Series of 14 Cases

Original language description

Spindle cell rhabdomyosarcomas (SCRMS), recognized by the 2020 WHO Classification of Tumors of Soft Tissue and Bone as a distinct entity, comprise a family of malignant skeletal muscle tumors sharing spindle cell morphology. To date, members of this family include 1) MyoD1-mutated spindle cell/sclerosing RMS (SCRMS/SRMS), 2) intraosseous SCRMS with FET::TFCP2 or MEIS1::NCOA2 fusions and 3) infantile congenital SCRMS harboring NCOA1/2 or VGLL3 rearrangements. A rare, emerging subtype of SCRMS has been reported to harbor recurrent ZFP64::NCOA3 fusions. We studied 14 cases of this rare SCRMS subtype. The tumors presented in 11 men and 3 women (median age: 39.5 years; range: 22-69) and involved the thigh (4), lower leg (2), gluteal soft tissues (2), abdominal wall (1), mediastinum (1), subperiosteal surface of 3(rd) rib (1), glottis (1), prostate (1), and pelvis (1). Morphologically, 11 tumors showed uniform spindle cell morphology with a fascicular architecture, while the remaining 3 tumors demonstrated focal or predominant round cell morphology. Extensive chondro-osseous differentiation was seen in 2 cases. By immunohistochemistry, tumors were variably positive for both desmin and MyoD1 (6 tumors), desmin, MyoD1 and myogenin (1 tumor), desmin alone (3 tumors of which only one was also tested for MyoD1), or MyoD1 alone (3 tumors). Smooth muscle actin was noted in 6 of 10 tested cases, and 2 of 5 tested cases showed ALK expression. A ZFP64::NCOA3 fusion was detected in 8 tumors, and a ZFP64::NCOA2 fusion in 6. Methylation studies showed all but one tested tumor to form a tight cluster, clearly separate from other RMS subtypes and non-RMS morphologic mimics. Clinical follow-up (10 of 14 cases; median: 35 months; range: 3-108 months) demonstrated local recurrence in 2 patients and distant metastases in 5 (median: 12 months; range: at presentation - 106 months). At the time of last follow-up, 5 patients were alive without evidence of disease, 3 patients were alive with disease, and 2 patients died of disease at 34 and 108 months. We conclude that SCRMS with ZFP64::NCOA2/3 fusions represent a distinct, clinically aggressive sarcoma, characterized by fascicular and sometimes round cell morphology, occasional chondro-osseous differentiation and variable skeletal muscle marker expression. Recognition of this emerging subtype of SCRMS may have prognostic and therapeutic implications.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30109 - Pathology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Modern Pathology

ISSN

0893-3952

e-ISSN

1530-0285

Volume of the periodical

38

Issue of the periodical within the volume

12

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

100906

UT code for WoS article

001621399500001

EID of the result in the Scopus database

2-s2.0-105021519043